CRISPR-Cas knockout of miR21 reduces glioma growth

被引：20

作者：

Nieland, Lisa ^{[1
,2
,3
]}

van Solinge, Thomas S. ^{[1
,2
]}

Cheah, Pike See ^{[1
,2
,4
]}

Morsett, Liza M. ^{[5
,6
]}

El Khoury, Joseph ^{[5
,6
]}

Rissman, Joseph, I ^{[7
,8
]}

Kleinstiver, Benjamin P. ^{[7
,8
,9
]}

Broekman, Marike L. D. ^{[1
,2
,3
,10
]}

Breakefield, Xandra O. ^{[1
,2
]}

Abels, Erik R. ^{[1
,2
,11
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Neurosci Program, Boston, MA 02129 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Neurosci Program, Boston, MA 02129 USA

[3] Leiden Univ, Dept Neurosurg, Med Ctr, NL-2300 RC Leiden, Netherlands

[4] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Human Anat, Serdang 43400, Malaysia

[5] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA

[6] Harvard Med Sch, Boston, MA 02129 USA

[7] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02115 USA

[8] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA

[9] Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA

[10] Haaglanden Med Ctr, Dept Neurosurg, NL-2512 VA The Hague, Netherlands

[11] Leiden Univ, Dept Cell & Chem Biol, Med Ctr, NL-2300 RC Leiden, Netherlands

来源：

MOLECULAR THERAPY-ONCOLYTICS | 2022年 / 25卷

关键词：

SUBCELLULAR-LOCALIZATION; GLIOBLASTOMA-MULTIFORME; TARGETING MIR-21; DOWN-REGULATION; IN-VIVO; EXPRESSION; MICRORNA; CDC25A; PROMOTES; PROTEIN;

D O I：

10.1016/j.omto.2022.04.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Non-coding RNAs, including microRNAs (miRNAs), support the progression of glioma. miR-21 is a small, non-coding transcript involved in regulating gene expression in multiple cellular pathways, including the regulation of proliferation. High expression of miR-21 has been shown to be a major driver of glioma growth. Manipulating the expression of miRNAs is a novel strategy in the development of therapeutics in cancer. In this study we aimed to target miR-21. Using CRISPR genome-editing technology, we disrupted the miR-21 coding sequences in glioma cells. Depletion of this miRNA resulted in the upregulation of many downstream miR-21 target mRNAs involved in showed reduced migration, invasion, and proliferation in vitro. In immunocompetent mouse models, miR-21 knockout tumors showed reduced growth resulting in an increased overall survival. In summary, we show that by knocking out a key miRNA in glioma, these cells have decreased proliferation capacity both in vitro and in vivo. Overall, we identified miR-21 as a potential target for CRISPR-based therapeutics in glioma.

引用

页码：121 / 136

页数：16

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